keyword
MENU ▼
Read by QxMD icon Read
search

Population pk

keyword
https://www.readbyqxmd.com/read/28239897/population-pharmacokinetics-of-rituximab-in-patients-with-diffuse-large-b-cell-lymphoma-and-association-with-clinical-outcome
#1
S Rozman, I Grabnar, S Novaković, A Mrhar, B J Novaković
AIMS: Pharmacokinetic (PK) studies suggest that there is a room for improvement in clinical use of rituximab through more individualized treatment. The objective of this study was to characterize rituximab PK in 29 newly diagnosed patients with diffuse large B-cell lymphoma treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine and methylprednisolone every three weeks. We also evaluated the association of rituximab PK with clinical outcome. METHODS: Rituximab serum levels were determined by enzyme-linked immunosorbent assay and evaluated by a population PK analysis applying non-linear mixed effects modelling...
February 27, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28239368/connection-of-nicotine-to-diet-induced-obesity-and-non-alcoholic-fatty-liver-disease-cellular-and-mechanistic-insights
#2
REVIEW
Amiya P Sinha-Hikim, Indrani Sinha-Hikim, Theodore C Friedman
Non-alcoholic fatty liver disease (NAFLD) poses a serious health hazard affecting 20-40% of adults in the general population in the USA and over 70% of the obese and extremely obese people. In addition to obesity, nicotine is recognized as a risk factor for NAFLD, and it has been reported that nicotine can exaggerate obesity-induced hepatic steatosis. The development of NAFLD has serious clinical complications because of its potential progression from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28230171/impact-of-genetic-variation-on-human-camkk2-regulation-by-ca-2-calmodulin-and-multisite-phosphorylation
#3
Matthew T O'Brien, Jonathan S Oakhill, Naomi X Y Ling, Christopher G Langendorf, Ashfaqul Hoque, Toby A Dite, Anthony R Means, Bruce E Kemp, John W Scott
The Ca(2+)-calmodulin dependent protein kinase kinase-2 (CaMKK2) is a key regulator of neuronal function and whole-body energy metabolism. Elevated CaMKK2 activity is strongly associated with prostate and hepatic cancers, whereas reduced CaMKK2 activity has been linked to schizophrenia and bipolar disease in humans. Here we report the functional effects of nine rare-variant point mutations that were detected in large-scale human genetic studies and cancer tissues, all of which occur close to two regulatory phosphorylation sites and the catalytic site on human CaMKK2...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224231/nc-6004-phase-i-study-in-combination-with-gemcitabine-for-advanced-solid-tumors-and-population-pk-pd-analysis
#4
Toshihiko Doi, Tetsuya Hamaguchi, Kohei Shitara, Satoru Iwasa, Yasuhiro Shimada, Mitsunori Harada, Kenichiro Naito, Naoto Hayashi, Atsuhiro Masada, Atsushi Ohtsu
OBJECTIVES: This study was an open-label phase I study to confirm the safety and tolerability of NC-6004 in combination with gemcitabine in Japanese patients with advanced solid tumors and to assess the PK effects of NC-6004 monotherapy. METHODS: This phase I study used a 3 + 3 design to determine the maximum tolerated dose (MTD) and recommended dose of NC-6004 combined with gemcitabine. Safety and pharmacokinetics were assessed. The administration of NC-6004 alone was started at 60 mg/m(2) every treatment cycle (21 days per cycle)...
February 21, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28223378/population-pharmacokinetic-analysis-of-doripenem-after-intravenous-infusion-in-korean-patients-with-acute-infections
#5
Dong-Hwan Lee, Yong Kyun Kim, Kyubok Jin, Myoung Joo Kang, Young-Don Joo, Yang Wook Kim, Young Soo Moon, Jae-Gook Shin, Sungmin Kiem
We investigated population pharmacokinetics (PK) of doripenem in Korean patients with acute infections, and determined an appropriate dosing regimen using a Monte-Carlo simulation for predicting pharmacodynamics (PD). Patients (n = 37) with a creatinine clearance (CLCR) of 20∼50 mL/min or >50 mL/min who received a 250-mg or 500-mg dose of doripenem over the course of one hour every eight hours, respectively, were included in this study. Blood samples were taken pre-dose and 0 h, 0.5 h, and 4-6 h after the fourth infusion...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28223227/mitogen-activated-protein-kinases-as-therapeutic-targets-for-asthma
#6
REVIEW
MirHojjat Khorasanizadeh, Mahsa Eskian, Erwin W Gelfand, Nima Rezaei
Corticosteroid-resistant asthmatics, although comprising only a portion of the asthma population, account for most of the morbidity, mortality and economic burden associated with asthma. Moreover, corticosteroids are not effective inhibitors of airway remodeling changes, and their long-term use is associated with debilitating systemic side effects. Therefore, potent and safe novel therapeutic alternatives, targeting basic pathophysiological mechanisms responsible for the severe asthmatic phenotype are urgently needed...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28220555/population-pharmacokinetic-characterization-of-bay-81-8973-a-full-length-recombinant-factor-viii-lessons-learned-importance-of-including-samples-with-factor-viii-levels-below-the-quantitation-limit
#7
D Garmann, S McLeay, A Shah, P Vis, M Maas Enriquez, B A Ploeger
INTRODUCTION: The pharmacokinetics (PK), safety and efficacy of BAY 81-8973, a full-length, unmodified, recombinant human factor VIII (FVIII), were evaluated in the LEOPOLD trials. AIM: The aim of this study was to develop a population PK model based on pooled data from the LEOPOLD trials and to investigate the importance of including samples with FVIII levels below the limit of quantitation (BLQ) to estimate half-life. METHODS: The analysis included 1535 PK observations (measured by the chromogenic assay) from 183 male patients with haemophilia A aged 1-61 years from the 3 LEOPOLD trials...
February 20, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28217242/investigating-state-restriction-in-fluorescent-protein-fret-using-time-resolved-fluorescence-and-anisotropy
#8
Thomas S Blacker, WeiYue Chen, Edward Avezov, Richard J Marsh, Michael R Duchen, Clemens F Kaminski, Angus J Bain
Most fluorescent proteins exhibit multiexponential fluorescence decays, indicating a heterogeneous excited state population. FRET between fluorescent proteins should therefore involve multiple energy transfer pathways. We recently demonstrated the FRET pathways between EGFP and mCherry (mC), upon the dimerization of 3-phosphoinositide dependent protein kinase 1 (PDK1), to be highly restricted. A mechanism for FRET restriction based on a highly unfavorable κ(2) orientation factor arising from differences in donor-acceptor transition dipole moment angles in a far from coplanar and near static interaction geometry was proposed...
January 26, 2017: Journal of Physical Chemistry. C, Nanomaterials and Interfaces
https://www.readbyqxmd.com/read/28216623/development-of-a-novel-individualized-warfarin-dose-algorithm-based-on-a-population-pharmacokinetic-model-with-improved-prediction-accuracy-for-chinese-patients-after-heart-valve-replacement
#9
Yu-Bin Zhu, Xian-Hua Hong, Meng Wei, Jing Hu, Xin Chen, Shu-Kui Wang, Jun-Rong Zhu, Feng Yu, Jian-Guo Sun
The gene-guided dosing strategy of warfarin generally leads to over-dose in patients at doses lower than 2 mg/kg, and only 50% of individual variability in daily stable doses can be explained. In this study, we developed a novel population pharmacokinetic (PK) model based on a warfarin dose algorithm for Han Chinese patients with valve replacement for improving the dose prediction accuracy, especially in patients with low doses. The individual pharmacokinetic (PK) parameter - apparent clearance of S- and R-warfarin (CLs) was obtained after establishing and validating the population PK model from 296 recruited patients with valve replacement...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28213961/chrysin-induces-death-of-prostate-cancer-cells-by-inducing-ros-and-er-stress
#10
Soomin Ryu, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Chrysin is a natural flavone found in numerous plant extracts, honey and propolis that has multiple biological activities including anti-cancer effects. Understanding of biological mechanisms mediated in response to chrysin in cancerous cells may provide novel insight into chemotherapeutic approaches with reduced side effects in cancers. In the present study, we investigated functional roles of chrysin in progression of prostate cancer cells using DU145 and PC-3 cell lines. The results showed that chrysin induced apoptosis of cells evidenced by DNA fragmentation and increasing the population of both DU145 and PC-3 cells in the sub-G1 phase of the cell cycle...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213941/population-pharmacokinetic-and-exposure-simulation-analysis-for-cediranib-azd2171-in-pooled-phase-i-ii-studies-in-patients-with-cancer
#11
Jianguo Li, Nidal Al-Huniti, Anja Henningsson, Weifeng Tang, Eric Masson
AIMS: A population pharmacokinetic (PPK) model was developed for cediranib to simulate cediranib exposure for different doses, including co-medication with strong UGT/Pgp inducers such as rifampicin, in cancer patients. METHODS: Plasma concentrations and covariates from 625 cancer patients after single or multiple oral cediranib administrations ranging from 0.5 to 90 mg in 19 Phase I and II studies were included in the analysis. Stepwise covariate modelling was used to develop the PPK model...
February 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28209738/optogenetic-low-frequency-stimulation-of-specific-neuronal-populations-abates-ictogenesis
#12
Zahra Shiri, Maxime Lévesque, Guillaume Etter, Frédéric Manseau, Sylvain Williams, Massimo Avoli
Despite many advances made in understanding the pathophysiology of epileptic disorders, seizures remain poorly controlled in approximately one third of mesial temporal lobe epilepsy patients. Here, we established the efficacy of cell type-specific low-frequency stimulation (LFS) in controlling ictogenesis in the mouse entorhinal cortex (EC) in an in vitro brain slice preparation. Specifically, we used 1 Hz optogenetic stimulation of Ca(2+)/calmodulin-dependent protein kinase II-positive principal cells as well as of parvalbumin- or somatostatin-positive interneurons to study the effects of such repetitive activation on epileptiform discharges induced by 4-aminopyridine...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28202004/a-phase-ii-study-to-evaluate-ly2603618-in-combination-with-gemcitabine-in-pancreatic-cancer-patients
#13
Berta Laquente, Jose Lopez-Martin, Donald Richards, Gerald Illerhaus, David Z Chang, George Kim, Philip Stella, Dirk Richel, Cezary Szcylik, Stefano Cascinu, G L Frassineti, Tudor Ciuleanu, Karla Hurt, Scott Hynes, Ji Lin, Aimee Bence Lin, Daniel Von Hoff, Emiliano Calvo
BACKGROUND: The aim of this study was to determine whether checkpoint kinase 1 inihibitor (CHK1), LY2603618, and gemcitabine prolong overall survival (OS) compared to gemcitabine alone in patients with unresectable pancreatic cancer. METHODS: Patients with Stage II-IV locally advanced or metastatic pancreatic cancer were randomized (2:1) to either 230 mg of LY2603618/1000 mg/m(2) gemcitabine combined or 1000 mg/m(2) gemcitabine alone. OS was assessed using both a Bayesian augment control model and traditional frequentist analysis for inference...
February 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28199964/blockade-of-rho-associated-protein-kinase-rock-inhibits-the-contractility-and-invasion-potential-of-cancer-stem-like-cells
#14
Srisathya Srinivasan, Vandhana Ashok, Sagarajit Mohanty, Alakesh Das, Sreya Das, Sushant Kumar, Shamik Sen, Rahul Purwar
Recent studies have implicated the roles of cancer stem like cells (CSCs) in cancer metastasis. However, very limited knowledge exists at the molecular and cellular level to target CSCs for prevention of cancer metastasis. In this study, we examined the roles of contractile dynamics of CSCs in cell invasion and delineated the underlying molecular mechanisms of their distinct cell invasion potential. Using de-adhesion assay and atomic force microscopy, we show that CSCs derived from melanoma and breast cancer cell lines exhibit increased contractility compared to non-CSCs across all tumor types...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197625/different-effect-of-resveratrol-to-induction-of-apoptosis-depending-on-the-type-of-human-cancer-cells
#15
Michinori Takashina, Sayaka Inoue, Kei Tomihara, Kengo Tomita, Kohshi Hattori, Qing-Li Zhao, Tokiko Suzuki, Makoto Noguchi, Wakana Ohashi, Yuichi Hattori
The effect of resveratrol on various human cancer cells was investigated with special focus on apoptotic cell death, in an attempt to further characterize its mechanism of action. There were great differences in the anti-viability effect of resveratrol between different types of human cancer cells. While the inhibition of cell viability by resveratrol was marked in U937 and MOLT-4 leukemia cells, resveratrol moderately inhibited cell viability in MCF-7 breast, HepG2 liver, and A549 lung cancer cells, and the effect was slight on cell viability in Caco-2, HCT116, and SW480 colon cancer cells...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28182011/tak1-regulates-resident-macrophages-by-protecting-lysosomal-integrity
#16
Yosuke Sakamachi, Sho Morioka, September R Mihaly, Giichi Takaesu, Julie F Foley, Michael B Fessler, Jun Ninomiya-Tsuji
Hematopoietic cell survival and death is critical for development of a functional immune system. Here, we report that a protein kinase, TAK1, is selectively required for resident macrophage integrity during embryogenesis. Hematopoietic lineage-specific deletion of Tak1 gene (Tak1(HKO)) caused accumulation of cellular debris in the thymus in perinatal mice. Although no overt alteration in thymocytes and blood myeloid populations was observed in Tak1(HKO) mice, we found that thymic and lung macrophages were diminished...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28181511/natriuretic-peptide-receptor-b-modulates-the-proliferation-of-the-cardiac-cells-expressing-the-stem-cell-antigen-1
#17
Stéphanie Rignault-Clerc, Christelle Bielmann, Lucas Liaudet, Bernard Waeber, François Feihl, Nathalie Rosenblatt-Velin
Brain Natriuretic Peptide (BNP) injections in adult "healthy" or infarcted mice led to increased number of non-myocyte cells (NMCs) expressing the nuclear transcription factor Nkx2.5. The aim of this study was to identify the nature of the cells able to respond to BNP as well as the signaling pathway involved. BNP treatment of neonatal mouse NMCs stimulated Sca-1(+) cell proliferation. The Sca-1(+) cells were characterized as being a mixed cell population involving fibroblasts and multipotent precursor cells...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28178895/repetitive-urine-and-blood-sampling-in-neonatal-and-weaned-piglets-for-pharmacokinetic-and-pharmacodynamic-modelling-in-drug-discovery-a-pilot-study
#18
Elke Gasthuys, Stijn Schauvliege, Thomas van Bergen, Joske Millecam, Ilaria Cerasoli, Ann Martens, Frank Gasthuys, Tim Vandecasteele, Pieter Cornillie, Wim Van den Broeck, Filip Boyen, Siska Croubels, Mathias Devreese
Piglets are considered to be suitable animal models for predicting the pharmacokinetics and pharmacodynamics (PK/PD) of test drugs for potential use in the paediatric population. Such PK/PD studies require multiple blood and urine samplings. The goal of the present study was to determine a suitable blood collection strategy applicable in the youngest age categories of six days, four weeks and eight weeks of age, as well as a urine collection technique for male piglets in the same age categories. Blood was collected either by a surgically-placed jugular vein catheter (six days old [ n = 4] and four weeks old [ n = 2] piglets) or by direct venepuncture of the jugular vein (four weeks old [ n = 2] and eight weeks old [ n = 4] piglets)...
January 1, 2017: Laboratory Animals
https://www.readbyqxmd.com/read/28174315/a-novel-phosphoregulatory-switch-controls-the-activity-and-function-of-the-major-catalytic-subunit-of-protein-kinase-a-in-aspergillus-fumigatus
#19
E Keats Shwab, Praveen R Juvvadi, Greg Waitt, Erik J Soderblom, M Arthur Moseley, Nathan I Nicely, Yohannes G Asfaw, William J Steinbach
: Invasive aspergillosis (IA), caused by the filamentous fungal pathogen Aspergillus fumigatus, is a major cause of death among immunocompromised patients. The cyclic AMP/protein kinase A (PKA) signaling pathway is essential for hyphal growth and virulence of A. fumigatus, but the mechanism of regulation of PKA remains largely unknown. Here, we discovered a novel mechanism for the regulation of PKA activity in A. fumigatus via phosphorylation of key residues within the major catalytic subunit, PkaC1...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28173838/osteoarthritis-associated-basic-calcium-phosphate-crystals-activate-membrane-proximal-kinases-in-human-innate-immune-cells
#20
Emma M Corr, Clare C Cunningham, Laura Helbert, Geraldine M McCarthy, Aisling Dunne
BACKGROUND: Osteoarthritis (OA) is a chronic debilitating joint disorder of particularly high prevalence in the elderly population. Intra-articular basic calcium phosphate (BCP) crystals are present in the majority of OA joints and are associated with severe degeneration. They are known to activate macrophages, synovial fibroblasts, and articular chondrocytes, resulting in increased cell proliferation and the production of pro-inflammatory cytokines and matrix metalloproteases (MMPs)...
February 7, 2017: Arthritis Research & Therapy
keyword
keyword
57095
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"